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Seladelpar provides safe, potent anti-cholestatic effect in PBC
SAN FRANCISCO — Results from a phase 2 study showed that daily treatment with seladelpar for primary biliary cholangitis was safe and maintained a potent anti-cholestatic effect after 52 weeks, according to data presented at The Liver Meeting 2018.
“Although it’s rare, it’s estimated that one in 1,000 women over the age of 40 are affected by PBC,” Christopher L. Bowlus, MD, from the University of California Davis Medical Center, said in his presentation. “The pathogenesis of PBC is an immune-mediated destruction of the biliary epithelial cells of intrahepatic bile ducts leading to chronic cholestasis, fibrosis, and cirrhosis and its complications.”
The study comprised 119 patients with either an inadequate response to ursodeoxycholic acid or an intolerance to UDCA and had an alkaline phosphatase (AP) higher than 1.67 times the upper limit of normal.
Bowlus noted that while patients who have an inadequate response or intolerance to UDCA can receive secondary treatment with Ocaliva (obeticholic acid, Intercept Pharmaceuticals). However, approximately half of patients who receive obeticholic acid still have an inadequate response and obeticholic acid can worsen pruritis.
“Therefore, there is a significant need for new therapies that have improved efficacy and improved tolerability,” Bowlus said.
The researchers randomly assigned patients to receive either 5 mg or 10 mg of seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist. At 12 weeks, patients in the 5 mg group could increase to 10 mg.
As of July 2018, 17 patients in each dose group completed 52 weeks of treatment. Overall, 59% in the 5 mg group and 71% in the 10 mg group achieved a decrease in AP to less than 1.67 times the upper limit of normal. AP decreased by 47% in the 5 mg group and 46% in the 10 mg group. AP normalization occurred in 24% of the 5 mg group and 29% of the 10 mg group.
Additionally, median alanine aminotransferase levels decreased by 31% in the 5 mg group and 33% in the 10 mg group and median visual analogue scale for the measurement of pruritus decreased by 30% in the 5 mg group and 66% in the 10 mg group.
The researchers did not consider any of the 11 observed serious adverse events related to treatment. One discontinuation for a grade 1 gastroesophageal reflux was deemed related to seladelpar.
“Overall, seladelpar was safe, well-tolerated and was not associated with pruritus,” Bowlus said. “These data have resulted in the initiation of a 52-week phase 3 global PBC study of seladelpar titled ENHANCE. Hopefully, this will confirm these results.” – by Talitha Bennett
Bowlus CL, et al. Abstract LB-3. Presented at: The Liver Meeting 2018; Nov. 9-13, 2018; San Francisco.
Disclosure: Bowlus reports financial connections with Allergan, Arena, BiomX, Bristol-Myers Squibb, Contatus, Cymabay, Eli Lilly, Genkyotex, Gilead, GlaxoSmithKline, Intercept Pharmaceuticals, JKB Taiwan, NGM Bio, Novartis, Takeda and TARGET Pharmaceuticals.